IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression.

Abstract

The effects of interferon-tau (IFN-tau) on tumor suppressor factors and virus oncoprotein expression were compared with two other type I IFN in human papillomavirus (HPV-16)-transformed cells. Nontumorigenic human keratinocytes, HuKc/HPV-16d-2C (d-2C), treated with recombinant human IFN-alpha2a (Roferon), a human recombinant alpha IFN hybrid, alpha B/D (IFN-alphaB/D), or ovine IFN-tau were evaluated for their effects on the levels of E6 and E7 expression. IFN-tau was comparable to IFN-alpha2a in decreasing intracellular levels of E6 and E7, and IFN-alphaB/D was more effective than IFN-a2a in suppressing E7 levels. All three IFN were capable of increasing the cellular concentration of wild-type p53 tumor suppressor with the magnitude IFN-tau > IFN-alpha2a > IFN-alphaB/D. Increases in p53 concentrations correlated with the observed decreases in E6 mRNA and protein levels. The antiviral effects observed in this study reveal that IFN-tau has potent antipapillomavirus activity. Sequences/structures unique to IFN-tau could allow for alternative IFN/receptor interactions and may explain the differences in biologic function.

• Authors: J A Johnson, H K Hochkeppel, J D Gangemi
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 19 Issue 10 Pg. 1107-16 (Oct 1999) ISSN: 1079-9907 [Print] United States
• PMID: 10547150 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• E6 protein, Human papillomavirus type 16
• Interferon Type I
• Interferon alpha-2
• Interferon-alpha
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• Pregnancy Proteins
• Recombinant Proteins
• Repressor Proteins
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• interferon tau
• oncogene protein E7, Human papillomavirus type 16

Topics

• Antiviral Agents (therapeutic use)
• Cell Division (drug effects)
• Cell Line, Transformed
• Depression, Chemical
• Gene Expression Regulation, Viral (drug effects)
• Humans
• Interferon Type I (therapeutic use)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Keratinocytes (drug effects, metabolism)
• Oncogene Proteins, Viral (genetics)
• Papillomaviridae
• Papillomavirus E7 Proteins
• Pregnancy Proteins (therapeutic use)
• Recombinant Proteins
• Repressor Proteins
• Retinoblastoma Protein (biosynthesis)
• Tumor Suppressor Protein p53 (metabolism)